The effects of galantamine on nicotine withdrawal-induced deficits in contextual fear conditioning in C57BL/6 mice

Derek S. Wilkinson, Thomas J. Gould

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Current smoking cessation aids are relatively ineffective at maintaining abstinence during withdrawal. Nicotine withdrawal is associated with a variety of symptoms including cognitive deficits and targeting these deficits may be a useful strategy for maintaining abstinence. Galantamine is an acetylcholinesterase inhibitor and allosteric modulator of nicotinic acetylcholine receptors (nAChRs) with cognitive enhancing effects that may alleviate cognitive deficits associated with nicotine withdrawal. The effects of galantamine on nicotine withdrawal-induced deficits in contextual fear conditioning in C57BL/6 mice were examined. An initial acute dose-response experiment revealed that 0.5 and 1. mg/kg galantamine had no effect on fear conditioning. To determine if galantamine would reverse nicotine withdrawal-related deficits in contextual fear conditioning, mice were implanted with osmotic mini-pumps that delivered chronic saline or 6.3. mg/kg/d nicotine for 12 days and then pumps were removed. Training and testing of fear conditioning occurred 24 and 48. h later, respectively. Nicotine withdrawal disrupted contextual fear conditioning, which was reversed with 1 but not 0.5. mg/kg galantamine. Across all conditions in both studies 2. mg/kg galantamine led to high levels of freezing that were likely due to nonspecific effects. The ability of galantamine to reverse nicotine withdrawal-deficits in contextual conditioning is likely mediated through enhanced levels of acetylcholine via inhibition of acetylcholinesterase, potentiation of hippocampal α4β2* nAChRs, or both. The present study suggests that acetylcholinesterase inhibitors and/or drugs that act as allosteric modulators of nAChRs might be targets for smoking cessation aids because they may alleviate withdrawal symptoms such as cognitive deficits that can lead to relapse.

Original languageEnglish (US)
Pages (from-to)53-57
Number of pages5
JournalBehavioural Brain Research
Volume223
Issue number1
DOIs
StatePublished - Sep 30 2011

Fingerprint

Galantamine
Nicotine
Inbred C57BL Mouse
Fear
Nicotinic Receptors
Cholinesterase Inhibitors
Smoking Cessation
Neurobehavioral Manifestations
Substance Withdrawal Syndrome
Aptitude
Acetylcholinesterase
Conditioning (Psychology)
Freezing
Acetylcholine
Recurrence

All Science Journal Classification (ASJC) codes

  • Behavioral Neuroscience

Cite this

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abstract = "Current smoking cessation aids are relatively ineffective at maintaining abstinence during withdrawal. Nicotine withdrawal is associated with a variety of symptoms including cognitive deficits and targeting these deficits may be a useful strategy for maintaining abstinence. Galantamine is an acetylcholinesterase inhibitor and allosteric modulator of nicotinic acetylcholine receptors (nAChRs) with cognitive enhancing effects that may alleviate cognitive deficits associated with nicotine withdrawal. The effects of galantamine on nicotine withdrawal-induced deficits in contextual fear conditioning in C57BL/6 mice were examined. An initial acute dose-response experiment revealed that 0.5 and 1. mg/kg galantamine had no effect on fear conditioning. To determine if galantamine would reverse nicotine withdrawal-related deficits in contextual fear conditioning, mice were implanted with osmotic mini-pumps that delivered chronic saline or 6.3. mg/kg/d nicotine for 12 days and then pumps were removed. Training and testing of fear conditioning occurred 24 and 48. h later, respectively. Nicotine withdrawal disrupted contextual fear conditioning, which was reversed with 1 but not 0.5. mg/kg galantamine. Across all conditions in both studies 2. mg/kg galantamine led to high levels of freezing that were likely due to nonspecific effects. The ability of galantamine to reverse nicotine withdrawal-deficits in contextual conditioning is likely mediated through enhanced levels of acetylcholine via inhibition of acetylcholinesterase, potentiation of hippocampal α4β2* nAChRs, or both. The present study suggests that acetylcholinesterase inhibitors and/or drugs that act as allosteric modulators of nAChRs might be targets for smoking cessation aids because they may alleviate withdrawal symptoms such as cognitive deficits that can lead to relapse.",
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The effects of galantamine on nicotine withdrawal-induced deficits in contextual fear conditioning in C57BL/6 mice. / Wilkinson, Derek S.; Gould, Thomas J.

In: Behavioural Brain Research, Vol. 223, No. 1, 30.09.2011, p. 53-57.

Research output: Contribution to journalArticle

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